TMEDA-Assisted Effective Direct Ortho Arylation of Electron-Deficient <i>N</i>‑Heteroarenes with Aromatic Grignard Reagents

In the addition of TMEDA in toluene, aryl Grignards could effectively and site-specifically ortho-arylate electron-deficient heteroarenes under mild conditions. This endeavor successfully changed the old low-yielding reaction, aryl Grignard addition to <i>N</i>-heteroarenes, into an efficient procedure for heterobiaryls. The combination of the inexpensive aryl Grignards, TMEDA, the cost-free air, no use of any transition-metal catalyst, the mild reaction conditions, and the high-yielding gram-scale results enables this new procedure to be cost-effective and potentially utilizable in industry

Aryl Bromides as Inexpensive Starting Materials in the Catalytic Enantioselective Arylation of Aryl Aldehydes: The Additive TMEDA Enhances the Enantioselectivity

We used aryl bromides as inexpensive starting materials to enantioselectively arylate aldehydes in one pot. Aryl bromides readily transfer aryls to aryllithiums with <i>n</i>-butyllithium, successively to triarylaluminums with aluminum chloride, and then to aryltitaniums with titanium isopropoxide. Finally aryltitaniums arylate aldehydes catalyzed by (<i>S</i>)-H₈-BINOL–Ti­(O<i>i</i>-Pr)₂ in excellent yields and enantioselectivities. The additive TMEDA evidently suppresses the racemic background reaction promoted by LiCl generated from salt metathesis. This procedure represents a cost-effective and operationally convenient method for enantioenriched diarylmethanols

Palladium-Catalyzed Allylic Substitution with (η⁶-Arene–CH₂Z)Cr(CO)₃-Based Nucleophiles

Although the palladium-catalyzed Tsuji–Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to “α-2-propenyl benzyl” motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η⁶-C₆H₅CHLiR)Cr(CO)₃ nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η⁶-toluene complexes, benzyl amine and ether derivatives (η⁶-C₆H₅CH₂Z)Cr(CO)₃ (Z = NR₂, OR) are also viable pronucleophiles, allowing C–C bond-formation α to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetalation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions